Epigenetic Mechanisms Underlying Cognitive Dysfunction in Parkinson's Disease: Current Evidence and Future Prospects Publisher Pubmed



Hasani F ; Kherad M E ; Sarasyabi M S ; Jazi K ; Ashkbari A ; Ahmadi P ; Heidarpour H ; Masrour M ; Khamaki S ; Rahmati R ; Surguchov A
Source: Brain and Behavior Published:2026

Abstract

Purpose: Epigenetics studies inheritable characteristics and lasting cellular changes that occur without alterations in the DNA sequence. This field is crucial for understanding how environmental factors interact with genes to influence memory, learning, and cognition. In the context of neurodegenerative disorders, particularly Parkinson's disease (PD), epigenetic mechanisms may help explain the molecular basis of cognitive impairment. The purpose of this review is to explore how epigenetic alterations affect gene expression and their potential role in cognitive dysfunction associated with PD. Method: This review synthesizes findings from existing literature on epigenetic mechanisms—including microRNA (miRNA) regulation, histone modification, and DNA methylation—in relation to neuronal function and cognitive processes in PD. Relevant studies were identified and analyzed to determine how these mechanisms may contribute to neuroinflammation, synaptic remodeling, and neuroprotection in PD. Findings: Epigenetic modifications can activate or silence gene expression by altering chromatin structure and protein interactions without changing the DNA sequence. In PD, such changes may influence genes involved in neuroinflammation, neuronal plasticity, and protective signaling pathways. Evidence suggests that dysregulation of DNA methylation, histone modification, and miRNA expression could be linked to the cognitive deficits observed in PD patients. However, the current body of research remains limited and heterogeneous. Conclusion: Epigenetic regulation represents a promising frontier for understanding cognitive impairment in PD. These mechanisms offer insights into how environmental and molecular factors interact to drive neurodegeneration. Further studies are needed to clarify the specific epigenetic alterations involved and to determine their potential as biomarkers or therapeutic targets for cognitive dysfunction in PD. © 2026 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.